ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
16962354 El-Jaick et al. (2007) sequenced TGIF1 in 435 individuals with HPE and detected 4 mutations in TGIF1, including a de novo nonsense mutation. The authors also recapitulate the functional studies by Gripp et al. (2000).
12522553 Aguilella et al. (2003) sequenced TGIF1 in 127 HPE individuals and found 2 mutations, including 1 nonsense mutation. The nonsense mutation was inherited from a father with hypotelorism and cleft lip, microsigns of HPE, but no ID.
22125506 Keaton et al. report seven individuals with mutations or deletions (large or focal) involving TGIF1 and also summarize data from other publications. Two frameshift LOF mutations (p.Phe86Serfs*13, p.Arg260Glyfs*58) and one "focal gene deletion" found in this study alone.

Evidence for Triplosenstive Phenotype

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.